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Comparative genomic characterization of Francisella tularensis strains belonging to low and high virulence subspecies

Champion, Mia D. and Zeng, Qiandong and Nix, Eli B. and Nano, Francis E. and Keim, Paul S and Kodira, Chinnappa D. and Borowsky, Mark and Young, Sarah and Koehrsen, Michael and Engels, Reinhard and Pearson, Matthew and Howarth, Clint and Larson, Lisa and White, Jared and Alvarado, Lucia and Forsman, Mats and Bearden, Scott W. and Sjoestedt, Anders and Titball, Richard and Michell, Stephen L. and Birren, Bruce and Galagan, James (2009) Comparative genomic characterization of Francisella tularensis strains belonging to low and high virulence subspecies. PLoS Pathogens, 5 (5). e1000459. ISSN 1553-7366

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Publisher’s or external URL: http://dx.doi.org/10.1371/journal.ppat.1000459


Tularemia is a geographically widespread, severely debilitating, and occasionally lethal disease in humans. It is caused by infection by a gram-negative bacterium, Francisella tularensis. In order to better understand its potency as an etiological agent as well as its potential as a biological weapon, we have completed draft assemblies and report the first complete genomic characterization of five strains belonging to the following different Francisella subspecies (subsp.): the F. tularensis subsp. tularensis FSC033, F. tularensis subsp. holarctica FSC257 and FSC022, and F. tularensis subsp. novicida GA99-3548 and GA99-3549 strains. Here, we report the sequencing of these strains and comparative genomic analysis with recently available public Francisella sequences, including the rare F. tularensis subsp. mediasiatica FSC147 strain isolate from the Central Asian Region. We report evidence for the occurrence of large-scale rearrangement events in strains of the holarctica subspecies, supporting previous proposals that further phylogenetic subdivisions of the Type B clade are likely. We also find a significant enrichment of disrupted or absent ORFs proximal to predicted breakpoints in the FSC022 strain, including a genetic component of the Type I restriction-modification defense system. Many of the pseudogenes identified are also disrupted in the closely related rarely human pathogenic F. tularensis subsp. mediasiatica FSC147 strain, including modulator of drug activity B (mdaB) (FTT0961), which encodes a known NADPH quinone reductase involved in oxidative stress resistance. We have also identified genes exhibiting sequence similarity to effectors of the Type III (T3SS) and components of the Type IV secretion systems (T4SS). One of the genes, msrA2 (FTT1797c), is disrupted in F. tularensis subsp. mediasiatica and has recently been shown to mediate bacterial pathogen survival in host organisms. Our findings suggest that in addition to the duplication of the Francisella Pathogenicity Island, and acquisition of individual loci, adaptation by gene loss in the more recently emerged tularensis, holarctica, and mediasiatica subspecies occurred and was distinct from evolutionary events that differentiated these subspecies, and the novicida subspecies, from a common ancestor. Our findings are applicable to future studies focused on variations in Francisella subspecies pathogenesis, and of broader interest to studies of genomic pathoadaptation in bacteria.

Item Type: Article
Publisher’s Statement: Creative Commons Public Domain declaration
ID number or DOI: 10.1371/journal.ppat.1000459
Keywords: agrobacterium-tumefaciens c58; Asia, Central; bacterial genetics; Bacterial pathogens; escherichia-coli; Evolution; francisella tularensis; live vaccine; outer-membrane; oxidative stress; pathogenicity island; pseudomonas-aeruginosa; response-regulator; secretion systems; tularemia; virulence (Microbiology)
Subjects: Q Science > QR Microbiology
NAU Depositing Author Academic Status: Faculty/Staff
Department/Unit: Research Centers > Center for Microbial Genetics and Genomics
Date Deposited: 16 Oct 2015 17:49
URI: http://openknowledge.nau.edu/id/eprint/1688

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